The most advanced system for understanding neural and molecular mechanisms of mammalian behavior is the effect of estradiol (E) on lordosis behavior by the female rat upon mounting by the male. Now we must begin to understand signals from important environmental sources other than the male which are permissive for female reproductive behavior. Luckily, thyroid hormones (T3) and their receptors (TR-alpha and TR-beta) are present in hypothalamus and offer exciting opportunities for study. At the molecular level, TR s can bind on DNA to estrogen response elements (EREs) and could influence E-stimulated synthetic events in neurons. At the biological level, changes in thyroid hormone in the blood can signal environmental temperature changes as well as stress. Thus, we will study the ability of thyroid hormones to alter the stimulation of lordosis behavior by estradiol, we will determine where in the nervous system these interactions occur, and we will analyze their molecular mechanisms in the brain of the female rat. Precise sites of T3-TR action will be determined both by blocking- maneuvers (antisense DNA, etc.) And by direct T3 microinjections. The behaviorally relevant genes, for progesterone receptor (PR) and for the enkephalin peptides (PPE) will elucidated in this connection. In doing these experiments we have the chance of illuminating how permissive environmental conditions are integrated with the main hormal and sensory determinants of a biologically crucial behavior. Medically, high thyroid hormone levels are well known in the clinic to cause irritability in women. More generally, discovering in neurobiological detail how hormonal or environmental alterations quite separate from ovarian changes influence a female s reproductive status will be important for fostering women s health.